Since benzimidazole compounds such as lansoprazole, omeprazole and rabeprazole have gastric acid secretion inhibitory activity, gastric mucoca protecting activity, etc., they are widely used as a peptic ulcer treating agent.
However, these compounds are inferior in stability, and are unstable to humidity, temperature and light. In particular, they are unstable to acids and, when formulated into an aqueous solution or a suspension, they become extremely unstable with lowering of pH.
In addition, stability in the form of preparations, i.e., tablets, powders, fine granules, capsules, etc. becomes lower than that of the compounds alone because of their strong interaction with other components in formulated preparations, and color change or degradation is observed upon production or storage of the preparations. In order to stabilize them, JP 62-277322 A discloses enteric granules, enteric fine granules, etc. obtained by blending a stabilizing agent composed of a basic inorganic salt of magnesium and/or calcium, followed by enteric coating.
Meanwhile, it is necessary to apply an enteric coating to a benzimidazole compound because the compound has such properties that it is hardly soluble in water and is unstable to acids. An enteric coating does not dissolve in a stomach containing a relatively larger amount of water, but dissolves in a small intestine containing a smaller amount of water, whereby a benzimidazole compound is dissolved and absorbed. That is, since a composition containing a benzimidazole compound is required to be rapidly disintegrated in a small intestine, granules which have a larger surface area, and which are more easily and rapidly disintegrated or dissolved than tablets are considered to be more desired.
In Examples specifically disclosed in JP 62-277322 A, the content of benzimidazole compound is about 6.3 to 11.5% based on the total enteric granules, and the capsule in which the granules are filled is No. 1 or 2. Pharmacy Vol. 50(3) 230-238 (1990) reports that smaller capsules are more easily administered in view of an appearance organoleptic test, and a limit of a capsule size which can be easily administered is No. 3. Then, No. 1 or 2 capsule may reduce compliance of patients, in particular, elderly patients who have difficulty in swallowing.